Notes

Bestrophinopathies: views upon scientific ailment, Bestrophin-1 perform as well as establishing therapies.
Bone loss materializes rapidly after immobilization or mechanical unloading. Hind limb injection with botulinum toxin A (BTX) is a highly reproducible animal model for disuse-induced bone loss. Here we describe an easy-to-use and enhanced version of the method employing multiple hind limb injections with BTX to induce a pervasive muscle paralysis and thereby disuse of the hind limb. Thirty-six 12-14-week-old female Wistar rats were stratified into three groups Baseline (Base), Control (Ctrl), and BTX. Disuse was achieved by injecting BTX directly into the right quadriceps femoris muscle, the hamstring muscles, and the posterior calf muscles. The rats were sacrificed after six weeks, and the right rectus femoris muscle and femur were isolated and analyzed. Hind limb disuse resulted in a significant and substantial loss of both muscle mass and bone mass. The loss of bone mass was accompanied by a reduction of trabecular bone mass and a deterioration of the trabecular micro-architecture with a reduction of trabecular thickness and trabecular number compared to Ctrl. In addition, the trabeculae changed from a more plate-like towards a more rod-like shape as indicated by an increase in the structure model index.•Multiple injections with BTX targeting muscles on both the anterior and posterior thigh and the calf ensure a uniform and pervasive muscle paralysis and hind limb disuse.•Hind limb injections with BTX results in a substantial loss of muscle and bone mass and deterioration of the trabecular micro-architecture.•The induction of hind limb disuse with BTX is highly reproducible.Investigation on the effects of disease-associated mutations on neurodevelopment is an essential approach to understand the molecular basis of neurological disorders and can be achieved by generating suitable animal models. However, some of the mutations preclude development of animal models, leaving cell-based models as the only options. Mouse embryonic stem cells (mESCs) are attractive because of the well-established technologies for introducing disease-associated mutations and the feasibility of investigating the abnormalities during different stages of neurogenesis. TCPOBOP mouse Importantly, such transgenic mESCs enable large-scale screening and identification of the most promising small molecules and/or drug candidates before undertaking expensive animal studies. Although neuronal differentiation from mESCs is one of the earliest methods to be developed, we observed that the published as well as publicly available methods did not yield neurons consistently. Here, we describe a 16-day differentiation protocol that consistently induced differentiation of mESCs into neurons. This step-wise protocol enables monitoring of the neuronal differentiation process at different stages as well as characterization using the markers for immature and mature neurons by using immunocytochemistry and quantitative real-time PCRs.•Development of a method for differentiating mouse ES cells into neurons.•Differentiating the mouse ES cells into embryoid bodies prior to induction of neuronal differentiation results in better neuron formation.De novo designed bioactive molecules, such as DNA, RNA and peptides, are utilized in increasingly diverse scientific, industrial and biomedical applications. Concatemerization of designed DNA, RNA and peptides may improve their stability, bioactivity and allow for gradual release of the bioactive molecule at the intended destination. In this context, we developed a new method enabling the formation of DNA concatemers for the production of artificial, repetitive genes, encoding concatemeric RNAs and proteins of any nucleotide and amino-acid sequence. The technology recruits the Type IIS SapI restriction endonuclease (REase) for assembling DNA fragments in an ordered head-to-tail-orientation. Alternatively, other commercially available SapI isoschizomers can be used LguI and thermostable BspQI. Four series of DNA vectors dedicated to the expression of newly formed, concatemeric open reading frames (ORFs), were designed and constructed to meet the technology needs. • Vector-enzymatic DNA fragment amplification technology. • Construction of DNA concatemers many times longer than those available with the use of current de novo gene synthesis methods. • Biosynthesis of protein tandem repeats with programmable function never seen in nature.We describe a 24-year-old pregnant woman at 34 weeks of gestation who presented to a community hospital with sharp chest pain radiating to her back. She was found to have a 6 cm ascending aortic aneurysm despite not having any established risk factors. She was transported by air ambulance to a tertiary-care hospital. She delivered a live female neonate via cesarean delivery. Her postpartum course was notable for multiple episodes of chest pain and multiple imaging studies that were read as negative for aortic dissection. Definitive valve surgery was postponed by the cardiothoracic surgeons to allow for recovery from severe preeclampsia, treatment of endometritis, and due to concerns for uterine bleeding while on anticoagulation during cardiopulmonary bypass. She was eventually transferred to another hospital in another state for valve-sparing surgery. During transport, she developed a pulmonary embolism, and after arrival an aortic dissection was confirmed. She received a mechanical aortic valve replacement and the aneurysm was repaired. She returned home and recovered without complication. A gene panel revealed a heterozygous pathogenic variant of the Filamin A gene. Aortic aneurysms during pregnancy are rare, and aortic dissections are more rare. We recommend expeditious surgical treatment, a heightened index of suspicion, and testing for a genetic cause of aneurysm when diagnosed in a pregnant or postpartum woman with no known risk factors.Recent reports suggest that arylamine N-acetyltransferases (NAT1 and/or NAT2) serve important roles in regulation of energy utility and insulin sensitivity. We investigated the interaction between diet (control vs. high-fat diet) and acetylator phenotype (rapid vs. slow) using previously established congenic rat lines (in F344 background) that exhibit rapid or slow Nat2 (orthologous to human NAT1) acetylator genotypes. Male and female rats of each genotype were fed control or high-fat (Western-style) diet for 26 weeks. We then examined diet- and acetylator genotype-dependent changes in body and liver weights, systemic glucose tolerance, insulin sensitivity, and plasma lipid profile. Male and female rats on the high fat diet weighed approximately 10% more than rats on the control diet and the percentage liver to body weight was consistently higher in rapid than slow acetylator rats. Rapid acetylator rats were more prone to develop dyslipidemia overall (i.e., higher triglyceride; higher LDL; and lower HDL), compared to slow acetylator rats.
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